The last decade has witnessed remarkable changes in our understanding of the pathogenesis of human disease. The role of nutrient metals and metal toxicants in elemental speciaiton has emerged as critical in this evolving conception of disease processes. The Chemical Analysis Facility Core (CAF) is requesting support to purchase a Nu Instruments ICP/two sector high resolution (HR) mass spectrometer coupled to a (Dionex) liquid chromatograph to replace an obsolete IC/ICP (Fisons) PQ3 quadrupole instrument. This instrument would markedly increase method sensitivity, improve isotopic ratio measurement precision, elimination most prevalent isobaric interferences, and reduce instrument down-time. The instrument will be placed in existent shared resource laboratories in EOHSI and staffed by personnel highly experience in the use of ion chromatography/inductively coupled plasma mass spectrometry. The CAF of the NIEHS Center at EOHSI will provide a resource available beyond the Institute and its parent universities while concurrently significantl improving its own elemental analytical capabilities. The CAF would represent a unique, state-of-the-art facility within the region for high resolution speciated elemental mass spectrometry. The CAF is essential component of the NIEHS Center of Excellence at the Environmental and Occupational Health Sciences Institute. It has earned a national reputation for its work in metal analysis and is recognized for both innovative methods development and for its high quality analytical services. As NIH-funded investigators from the Center and EOHSI increasingly explore the potential modulating properties of nutrient elements such as Ca, Mg, Fe and Zn, as well as micronutrient elements such as Mn, Cr, Cu and Se, they require detailed quantitative information on the metabolic process of these inorganic ions and related organo- metallic species. The requested instrument will meet those needs with greater precision, sensitivity and resolution than any commercial instrument. PUBLIC HEALTH RELEVANCE: To meet the needs of NIH investigators measuring concentrations of elements at ever lower concentrations while simultaneously requiring information on the chemical form or species of a metal, funds are requested to interface an ion chromatograph to a high resolution ICPMS. This instrument will be capable of measuring metals with greater precision, sensitivity and resolution in samples such as culture, blood, tissue and urine. These measurements are critical to those studying the nutritional or toxicological mechanisms of inorganic (metal) compounds. The proteins or small molecules that bind these metals provide more information about the biological process than just the quantity of the metal when understanding how they are metabolized. Relative to Public Health Statement: The requested instrument will be used to support scientists who study how toxic and nutritional elements interact with the human body. Being able to identify and quantify these metals will help to identify populations who are at risk from exposure and who are at risk form being deprived of key nutritional elements. In addition the mechanistic toxicology of the metals can be better understood by making the measurements of the chemical form as it undergoes metabolism in the human body. The requested instrument will allow us to make those measurements with greater precision and to lower levels than have previously been achieved.